5-[1-hydroxy-2-(1-methyl-3-phenylpropyl)aminoethyl]salicylamide a substance known as labetalol is a well known antihypertensive agent as disclosed in U.S. Pat. No. 4,012,444. Labetalol is a mixture of all four possible optically active stereoisomers which can be designated R,R; R,S; S,R; and S,S according to the Cahn-Ingold, Prelog system. (-)-5-[(R)-1-hydroxy-2-((R)-1-methyl-3-phenylpropyl)aminoethyl]salicylamid e, hereafter for convenience refered to as the R,R stereoisomer is of interest. It possesses unique properties compared with the other isomeric forms, and labetalol, enabling it to be used in the treatment of hypertension as discussed in detail in European Patent No. 79103473.9 Publication No. 9702. incorporated by reference herein. The R,R stereoisomer substantially free of the other stereoismers can be prepared by a series of process steps requiring chromatographic operations on diastereomeric intermediates in order to ensure the desired sterically pure final product is obtained.
Thus European Patent Application No. 79103473.9 Publication No. 9702 describes the stereoselective synthesis of the HCl acid addition salt of the R,R stereoisomer by a procedure involving the chromatographic separation of the desired isomer from a diastereomeric mixture.
We have now found that by employing certain stereospecific intermediates the R,R stereoisomer may conveniently be prepared by a process involving resolution of intermediates by salt formation instead of by chromatography.